InstaDeep has introduced Nucleotide Transformer v3 (NTv3), a multi-species genomics foundation model designed to enhance genomic prediction and design by connecting local motifs with megabase scale regulatory contexts. NTv3 operates at single-nucleotide resolution for 1 Mb contexts and integrates representation learning, functional track prediction, genome annotation, and controllable sequence generation into a single framework. The model builds on previous versions by extending sequence-only pretraining to longer contexts and incorporating explicit functional supervision and a generative mode, making it capable of handling a wide range of genomic tasks across multiple species. NTv3 employs a U-Net style architecture that processes very long genomic windows, utilizing a convolutional downsampling tower, a transformer stack for long-range dependencies, and a deconvolution tower for base-level resolution restoration. It tokenizes input sequences at the character level, maintaining a vocabulary size of 11 tokens. The model is pretrained on 9 trillion base pairs from the OpenGenome2 resource and post-trained with a joint objective incorporating self-supervision and supervised learning on functional tracks and annotation labels from 24 animal and plant species. This comprehensive training allows NTv3 to achieve state-of-the-art accuracy in functional track prediction and genome annotation, outperforming existing genomic foundation models. Beyond prediction, NTv3 can be fine-tuned as a controllable generative model using masked diffusion language modeling, enabling the design of enhancer sequences with specified activity levels and promoter selectivity. These designs have been validated experimentally, demonstrating improved promoter specificity and intended activity ordering. NTv3's ability to unify various genomic tasks and support long-range, cross-species genome-to-function inference makes it a significant advancement in genomics, providing a powerful tool for researchers and practitioners in the field. This matters because it enhances our understanding and manipulation of genomic data, potentially leading to breakthroughs in fields such as medicine and biotechnology.
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